Transplanted neural stem cells (NSCs) show a remarkable ability to migrate throughout the CNS, intermingle with host cells, and express foreign transgenes in vivo. Intriguingly, this inherent migratory property of NSCs emulates the migratory pattern of some brain tumors such as gliomas, characterized by invasive single cell migration. We postulate that the migratory properties of NSCs can be harnessed to disseminate therapeutic genes products to these invading brain tumor cells. Recent studies found that murine NSCs appear to target tumor cells in intracranial glioma rodent models. Implanted murine NSCs, genetically modified to express a reporter gene, distributed themselves extensively throughout the tumor bed and migrated in juxtaposition to aggressively advancing tumor cells, while continuing to stably express a foreign reporter gene. Proposed studies will confirm and characterize the migratory properties of human NSCs in the context of invasive rodent and human glioblastoma tumor cells (labeled with green fluorescence protein). Brain histological and immunocytochemical analysis will be used to determine the extent of NSC migration and transgene expression. These studies will provide proof of concept for the use of human NSCs as a novel, efficient delivery vehicle to target therapeutic genes and vectors to refractory, invasive brain tumors cells. PROPOSED COMMERCIAL APPLICATIONS: Human neural stem cells represent a compelling new technology platform with widespread therapeutic implications for the treatment of neurological diseases. Their transplantation, migration, differentiation, and gene expression properties can be exploited to treat neurodegenerative disorders, brain tumors, and other diseases. Demonstration of the clinical applicability, technical feasibility, and commercial viability of stem cell therapy is anticipated in the near future.